Diabetes mellitus is a very common disease which, in its severe juvenile-onset form, produces substantial morbidity and significantly shortens life. Evidence suggests that available treatment with insulin and diet fails to prevent the widespread, debilitating vascular lesions associated with diabetes. Although much remains to be learned about the pathophysiology of diabetes, transplantation of the pancreas represents one potential means of curing the condition that is worthy of serious investigation. Research has demonstrated the technical feasibility of pancreas transplantation, as well as endocrine function of pancreas allografts for short periods of time. However, because of the problems associated with immunologic rejection and immunosuppression therapy, it has not been possible to perform long-term studies of graft function and morphology, or to answer important questions about the effects of pancreatic duct ligation on islet cell function. Moreover, studies of exocrine function have not been feasible. Recent work in our laboratory has produced a consistently successful technique of heterotopic pancreaticoduodenal transplantation in rats. By using inbred rats, this experimental model provides a unique opportunity to perform long-term studies of endocrine function, morphology and effect on diabetes, to determine whether obstruction to secretory outflow causes autodigestion of the gland or adversely affects the islets of Langerhans, and to investigate exocrine function. Furthermore, the opportunity is provided to evaluate the influence of immunosuppression regimens on pancreas allografts between rats of diffefent strains. Should pancreas transplants prove to function effectively over long periods, their beneficial influence on the course of diabetes mellitus remains a crucial question. It is difficult to answer this question by human investigation because of the high risks and long time period required, and an animal model of spontaneous diabetes would greatly facilitate determination of this central issue. Such a model, the Chinese hamster, has been identified and extensively characterized recently, and we have developed a microvascular technique of pancreas transplantation in this small animal. The opportunity now exists for determining, in a relatively short period of time, the potential of pancreas transplantation for preventing and relieving diabetes mellitus and its widespread manifestations.